This project consists of six phases: (1) A series of semi-rigid analogs of dopamine as typified by 6,7-dihydroxytetranaphthalene and 5,6-hydroxytetranaphthalene were investigated on the dopamine vascular receptor. Only the 6,7-dihydroxytetranaphthalenes were active. N,N-dipropyl dopamine was found to be an active dopamine agonist, but differed from dopamine in lacking beta-adrenergic action on the heart. (2) Dopamine was localized in the kidney by a radiometric procedure. Higher quantities of dopamine were located in the cortex and levels of the catecholamine were decreased by denervation. (3) The prostaglandin antagonist, 7-oxo-prostanoic acid, was an antagonist of prostaglandin E2 and prostaglandin F2 in isolated canine and rabbit arteries. (4) A method of determining optimal experimental conditions for maintaining a viable primary isolated hepatocyte culture and the analytic procedures for determining the rate of bio-transformation of a number of substates was developed. (5) The stable isotope carbon-13 method as labeled in aminopyrine for use in breath analysis of 13CO2, was utilized. Ten patients with biopsy proven primary biliary cirrhosis were similar to normal subjects. In contrast, patients with severe alcoholic cirrhosis has essentially negligible N-demethylation of aminopyrine. (6) Statistical studies were initiated in several clinical investigations to improve the efficiency of trials, and to extend the analytical methods now available.